OF INTRACRANLAL MENINGIOMAS AFTER SURGICAL TREATMENT · a second primary meningioma. It is r possible in a given case to decide which responsible. FrequencyofRecurrence Inthe Oxfordseries,

J. Neurol. Neurosurg. Psychiat., 1957, 20, 22.

THE RECURRENCE OF INTRACRANLAL MENINGIOMASAFTER SURGICAL TREATMENT

BY

DONALD SIMPSONFrom the Department ofNeurological Surgery, Radcliffe Infirmary, Oxford

The meningiomas are justly considered to beamong those intracranial tumours most amenableto treatment, and if the difficulties, often formidable,attending their removal can be overcome, there isgood prospect of a permanent cure. However, inoccasional cases, late recurrences do take place, evenafter resections appearing entirely satisfactory to thesurgeon responsible. This is not a common mis-fortune, but neither is it rare enough to be negligible.Considerable interest attaches to the tumours whichrecur after seemingly adequate treatment. Theypresent important practical problems in prophylaxisand in management. And they are most instructiveas studies in the biology of the meningiomasgenerally.Most neurosurgeons have experienced the dis-

appointment of such recurrences. Horsley (1893),Ballance (1907), and Krause (1910-12), while stress-ing the innocence of the tumours they designatedfibromas, endotheliomas, or dural sarcomas, allmention their occasional unexpected recurrence.Initially, little importance was attached to theserecurrences, but as neurosurgical technique im-proved and the number of survivals increased, theyattracted more attention. Craig, in 1927, first em-phasized the variations in the natural history of themeningiomas, and separated a group whose histologyand behaviour he considered frankly malignant.Taylor (1928) also challenged contemporary belief inthe innocence of the meningiomas. It was, however,in the great monograph of Cushing (1938) that thebehaviour of the meningiomas and their dispositionto recur were most fully discussed. Cushing ap-parently began his surgical career with the convictionthat the meningiomas are highly benign tumours:he ultimately came to treat them with the greatestrespect, as prone to infiltrate locally and to recurfrom such infiltrations. In 43 of his 295 cases, re-operation for " actual or symptomatic" recurrencewas necessary, and 76 patients died at home withincompletely removed tumours. Cushing unfortu-nately does not state the incidence of recurrence

after operations which had appeared to him as totalremovals: but analysis of his tabulated cases suggeststhat it was not less than 15%. He and Eisenhardtpresented a complex histological classification,which was specifically intended as a guide to thebiological behaviour of the tumours, but theynevertheless recognized the limitations of the histo-logical assessment.

This monograph remains the prime source forany study of the meningiomas. Since its publication,there have been a number of reports on the moderntreatment of meningiomas; in most of these thedevelopment of recurrence is mentioned. There hasbeen at least one study devoted solely to this problem(Volynkin, 1955). Much has been written on thepathology of the meningiomas, and especially ontheir occasional malignancy. A review of the largebody of literature suggests, however, that there isstill difference of opinion on several questions offundamental importance.

(1) There is no agreement on the frequency orsignificance of recurrence. Very few contemporarysurgeons have given the incidence of recurrence intheir material. Olivecrona (Olivecrona, 1947;Hoessly and Olivecrona, 1955) thought that with hisparasagittal meningiomas the recurrence rate wasunder 10%; his figures are, however, admittedlyincomplete, since they do not comprehend patientsdying at home. Grant (1954) reported 13 delayeddeaths due to tumour growth in 219 cases, all after" incomplete removals ". He refers to these fatalitiesas deaths from recurrence, and very properly, sinceone may speak of a symptomatic recurrence evenafter an operation known to have been incomplete.But it is not possible to determine from his accountwhether these " incomplete removals " had beenrecognized as such initially, or whether they hadappeared complete resections at the original opera-tion. This is a crucial distinction. The same uncer-tainty vitiates (for this particular purpose) the reportof Horrax and Strain (1952), who mention ninefatal recurrences in 168 cases. Moreover, in neither

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RECURRENCE OF INTRACRANIAL MENINGIOMAS

report is it clear how many non-fatal recurrenceswere encountered. There is also great difference inthe emphasis attached to the problem: some pass itover as of little moment, while others, like Fincher(1954), lay very great weight on it.

(2) There is also much uncertainty as to the causesof recurrence, especially their relative importance.It is generally agreed that some meningiomas areclinically malignant, as witnessed by rapid growth,invasive tendency, and, rarely, extracranial meta-stasis. Winkelman, Cassel, and Schlesinger (1952)found 10 acceptable examples of metastasis, towhich may be added the cases reported by Christen-sen, Klaer, and Winblad (1949), Swingle (1949),Laymon and Becker (1949), Cross and Cooper(1952), Shozawa (1952), Zulch, Pompeu, and Pinto(1954), Rosen and Branch (1954), and Lima (1951),in all at least 19. But whether in practice clinicalrecurrences are more likely to result from the intrinsicmalignancy of the tumours, rather than from theinadequacy of the surgical resections, is still dis-putable.

(3) There is no unanimity on the biological sig-nificance attachable to the histological appearancesin a given tumour. Thus, Turner, Craig, andKernohan (1942) claim a close correlation betweenclinical course and histology, whereas FolkeHenschen (1955) found no constant relationship.The possibility that microscopic assessment may besupplemented by study of the angioarchitecture ofthe living tumour, as seen in angiograms, is alsocontroversial. If a definite assessment of the poten-tialities of a particular tumour could be made, andits liability to recur were considered high, thepropriety of carrying out a more radical resectionwould arise, and perhaps even of prophylacticirradiation, though these tumours are not generallyconsidered radio-sensitive (McWhirter and Dott,1955).Some of these differences of opinion are differences

only in emphasis without basic disagreement. Others,however, are more profound, and raise issues rele-vant to the operative treatment of the meningiomas.Moreover-and few writers have given this its dueprominence-a just appreciation of the natural his-tory of the disease is essential in post-operativemanagement. The likelihood that a given tumourwill recur must be kept in mind, because recurrentmeningiomas may present serious diagnostic diffi-culties. This is particularly so when the onlysymptom is epilepsy and the bulk of the tumour isinsufficient to distort the ventricular or arterialanatomy, as may occasionally be the case. It seemstherefore worth while to present the conclusionsderived from a study of the problem of recurrence

begun several years ago, out of concern at theapparent frequency of recurrence with meningiomas,especially those in the parasagittal group.

MaterialBetween April, 1938, and December, 1954, 242

cases of intracranial meningioma were treated in theDepartment of Neurological Surgery at the RadcliffeInfirmary, excluding patients with spinal and primaryintraorbital meningiomas. In all, the diagnosis wasconfirmed either at operation or at necropsy; in allsave two verification by microscopy has beenobtained and reviewed by the writer. These patientsare the basis of the investigation reported here. Theyare referred to as the Oxford series.When the analysis of this series was completed,

it was realized that the lack of any cases survivingmore than 17 years was a serious drawback. Forthis reason, the intracranial meningiomas treated bySir Hugh Cairns when in London, between 1928 and1938, have also been considered. There were 97 ofthese. However, they were found to constitute lesssatisfactory material. This was partly because ofdifficulties in following the patients up, and partlybecause the tumours seem to a degree a selectedgroup, malignant behaviour being unduly rare withthem. They have therefore been separately desig-nated as the London series, and only limited use hasbeen made of them.The material thus available can be examined from

two aspects. First, the analysis of the ultimate fatesof those patients surviving operation gives the inci-dence of recurrence and its practical significance.For this purpose, the survivors in both series havebeen considered, and their fates determined. Thiswas an unexpectedly difficult enterprise. It has beenpossible to trace all the cases of the Oxford series,though in two the information obtained is meagre.The patients in the London series were more elusive,many having been dispersed by the war, and 10have not been found. It is very probable that someof those still missing are living yet, but it seems bestto exclude them. Second, the pathological findings,both operative and at necropsy, in the Oxford serieshave been personally reviewed. Analysis of all thesegives a background against which the pathology ofthose tumours which have recurred can be studied.Clinical data relevant to the prophylaxis of recur-rence have been taken from the Oxford series, andare briefly considered in conclusion.

TerminologyAs far as possible Cushing's (1938) terminology

has been used. His method of regional classificationhas also been employed, save in that no separateidentification of the few peritorcular tumours has

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seemed needful. Table I shows the incidering to this system, with, for comparison,published by Cushing (1938) himself andcrona (1947). More controversial is the dwhat constitutes a meningioma. It is,merely a term of convenience, without ahistogenetic implication. Some pathologit to comprehend diffusely spreading non-i

TABLE IREGIONAL INCIDENCE

Site London Oxford CusiSite Series Series (19.

Posterior fossa 8 27 2iSubtemporal 1 8Sphenoid ridge

(a) global 14 32 3(b) enplaque 2 9 ii

Suprasellar 7 14 2iOlfactory groove 12 14 2!Convexity 20 47 5Parasagittal and peritorcular 27 80 7Faix 2 6Intraventricular 2 4Other 2 1

97 242Totals

339 29

malignant tumour (cf. Globus, Levin, a1944). Others narrow it by excludingblastic tumours (cf. Kernohan and Sa)Here, in an attempt to conform withclinical usage, the term is applied to thoscribed tumours with meningeal or choroiment, whose histology suggests, or is atpatible with, an origin from the cells of thevilli. This is to include tumours corendothelial cells, fibroblastic tumours,formative tumours, however anaplasticlinically malignant connective tissue tunbeen excluded because, though they wzgliomatous character nor metastatic, itpossible to say from what mesenchymalarose.

Finally, the term " recurrence " is usedclinical sense to imply the reappearance ofdue directly to tumour growth after a perintomatic relief. So used, it has no pzspecificity, and though of course such ausually means the continued growth ofpletely excised tumour, yet it may also bto cover patients whose symptoms returna second primary meningioma. It is rpossible in a given case to decide whichresponsible.

Frequency of RecurrenceIn the Oxford series, 235 cases came to

in the remainder, only diagnostic procec

DONALD SIMPSON

ace accord- carried out. Thirty (13%) died within six months.,the series This figure overestimates the real surgical mortality,I by Olive- since it comprehends a few patients dying from inter-efinition of current disease or continued tumour growth afterafter all, their discharge from hospital. But for the present

mny precise purpose, survivals of less than six months cannot be;ists extend considered as worth-while clinical remissions, andgliomatous they are therefore excluded. In the earlier London

series, the operative mortality was naturally greater,and only 70 patients survived more than six months.Of these, 10 are excluded because untraced, leaving

hing Olive- in the two series together 265 patients in whom the38) (1947) possibility of recurrence can arise.8 72 It seems that 55 of these patients have developed8 17 symptomatic recurrences, 44 in the Oxford series7 96 and 11 in the London series. It is true that histo-6 15 logical verification, from biopsy or necropsy, is8 429 46 lacking in 21 instances. These are mainly patients4 91 dying at home or in other centres, whose deaths7 62 were certified as due to intracranial tumour. Some4 186 6 doubt must arise as to the accuracy of such certifica-

tion. Hoessly and Olivecrona (1955), faced with the4 608 same problem, thought it impossible to sift the

deaths by recurrence from those due to unrelateddisease. I have, however, felt it wisest to accept the

nd Sheps, opinion of the attendant physician, amplified wherethe ang1o- possible by personal enquiry, though with someyre, 1952). reservations in four cases. To offset this possibilityi ordinary of error, it is very probable that several of the 10)se circum- cases untraced also died of recurrence. I believe,idal attach- therefore, that this estimate is substantially correct,least com- and that in the combined series the incidence ofarachnoid recurrence is about 21%.nposed of This is a high incidence, and becomes even higherand vaso- if cases treated recently are excluded. It is, however,ic. Two inflated by the inclusion of recurrence developingnours have after resections known to have been incomplete.ere not Of These are symptomatic recurrences as here defined,t was not but their significance is much less than that oftissue they recurrences after apparently complete removals, and

it is necessary to analyse the operative proceduresin a purely more minutely.symptoms Some were thought by the surgeon to be complete;od of sym- some were extensive but left aside small residua;athological some were frankly incomplete. From the veryrecurrence detailed descriptions recorded by Sir Hugh Cairns,an incom- Mr. J. Pennybacker, and their assistants, it is possiblee extended to identify five fairly distinct grades of operation.because of Grade I.-This is a macroscopically complete

process is removal of the tumour, with excision of its duralattachment, and of any abnormal bone. Where thetumour arises from the wall of a dural venous sinus,such an operation necessarily entails resection of

nni-rn; the sinus.Grade I1.-This denotes a macroscopically

upfz1 aitiuii

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complete removal of the tumour and of its visibleextensions, with endothermy coagulation (usually tothe point of charring) of its dural attachment.Grade m.-This denotes a macroscopically com-

plete removal of the intradural tumour, withoutresection or coagulation of its dural attachment, oralternatively, of its extradural extensions, e.g., aninvaded sinus or hyperostotic bone.Grade IV.-This denotes a partial removal, leaving

intradural tumour in situ.Grade V.-This is a simple decompression, with

or without biopsy.Such a subdivision may be thought over-

elaborate. But it is essential that some distinctionbetween operations of varying scope should be made,and this seems a convenient, even a natural, grading.It is of course true that the surgeon's assessment isnot always correct, especially with the deepertumours. However, the main purpose of this investi-gation is the study of the unforeseen, usually unfor-seeable, recurrence, and therefore the operativeimpression, sometimes modified by examination ofthe excised specimen, must be the standard.An operation of Grade I is radical treatment.

It was possible to carry out such operations withmost of the tumours of the cerebral (or cerebellar)convexity, since their dural attachments are access-ible and unrelated to a major venous sinus. Lessthan a quarter of the parasagittal and falx tumourswere so treated. With the parasagittal tumours anoperation of Grade I entailed resection of thesuperior longitudinal sinus, and usually a completeresection, although it was rarely found sufficient todo a marginal resection without total occlusion ofthe sinus. The dangers of resecting the patentsinus are well known. The primary tumours of thefalx, by definition, do not arise from the walls of thesagittal sinus and may never encroach on them; evenso, there is a natural reluctance to excise the freefalx opposite the striate cortex or the paracentrallobule. Grade I operations were very rarely possiblewith tumours of the sphenoidal ridge, posterior fossa,olfactory groove, and suprasellar region. In all, 90operations of this grade were carried out; in 81 casesthese were primary operations, and in nine opera-tions on recurrent tumours. There have been eightrecurrences after operations of this grade, sevenverified and one rather questionable.

Fig. 1 shows their regional distribution. Twotumours of the sphenoidal ridge recurred, althoughtheir dural attachments had been stripped off, andall suspicious bone nibbled away. Two para-sagittal meningiomas, one already recurrent afterless radical surgery, have recurred despite blockresection of sinus ar'd falx. Two tumours of the

cerebral convexity are thought to have recurred:in one the recurrence was verified at operation, butin the other, a case in the London series dying12 years after the original resection, there is somedoubt over the diagnosis. A tumour of the cere-bellar convexity has recurred twice. The incidenceeven after this radical procedure, which wouldappear to meet the surgical ideal for these tumours,is thus 9%. If cases treated in the last five yearsare excluded, the incidence is unchanged, becausetwo recent cases have already recurred. It is never-theless reasonable to assume that this figure of 9%is a minimum estimate, and that a few other tumoursin this group will eventually recur. The average timeelapsing between primary operation and confirma-tion of recurrence was 62 months in the verifiedcases, the longest interval being 131 years and theshortest 13 months.

Operations of Grade II are usually considered assatisfactory treatment. But it is clear that to rely onthe diathermy coagulation as a destructive agent isto admit an uncertain factor. One patient in theOxford series died in a road accident a year afterthe removal of an olfactory groove meningioma.Necropsy showed no visible tumour remnants. Thedural attachment, which had been carefully coagu-lated, was examined in serial sections, and no tumourcells were found. But in the underlying bone nestsof viable meningioma tissue were clearly seen. Forwhat it is worth, this suggests that the diathermycoagulation is able to deal efficiently with invasionof the dura mater, but that it will not sterilize anymore remote spread. And this accords with clinicalexperience.Grade II resections were carried out on 114 occa-

sions (107 primary operations and seven operationsfor recurrent tumours). Most of the parasagittalmeningiomas were so treated (Table II). Grade IIresection was the only radical procedure possiblewith the tumours of the olfactory groove, and with

TABLE 11RADICAL OPERATIONS AND INCIDENCE OFRECURRENCE IN DIFFERENT SITES (COMBINED

SERIES)

|_______Grade I Grade II

No. of No. of % No. of No. of %Site Opera- Recur- Recur- Opera- Recur- Recur-

tions rences rence tions rences rence

Parasagittal and 21 2 5 69 12 17falx

Convexity and in- 58 2 3-5 6 1 17traventricular (1 du-

bious)

Basal 11 4 36 39 5 13Sphenoidal ridge (7) (2) (10) (2)Subfrontal (1) (0) (13) (1)Subtemporal (0) (0) (1) (0)Posterior fossa (3) (2) (13) (2)

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DONALD SIMPSON

OPERATIONS OF

CASESSURVIV-ING:

> 6

GRADE

90- -MON

> 5 6 3YEARS

>lo 45YEARS

> 15YEARS

> 20YEARS

RECUR-RENCES

24

7+ 1

GRADEII

114

68

39

10I

14+4

GRADE GRADE RADEIII IV V

24 _

27

i

3

9I

3+4 8+ 12

2

7+

UNVERIFIED LZ

FIcG. I.-Diagram showing operation grading, survival time, and frequency of recurrence in the combined Oxford and London series.All are patients surviving six months or more and known to have been alive and well at or after Christmas, 1953.

all save one of the suprasellar tumours: this was sobecause the removal of their dural attachmentswould have laid bare the ethmoid air cells. It wasalso the procedure of expediency with most of thetumours of the sphenoidal ridge and of the posteriorfossa, including all those in the cerebello-pontineangle that could be removed satisfactorily.

There were 18 recurrences after such resections.Fourteen have been confirmed at operation ornecropsy; in the other four the diagnosis rests onclinical findings-fairly securely in three, but muchless so in the fourth. This gives a recurrence rate of16%, or 19% if cases treated in the last five yearsare excluded. The average time elapsing before con-firmation of recurrence (in verified cases only) was59 months, the extremes being 13 years and 26months. It is worth noting that of all the recurrencesafter operations of Grades I and II, only four camewith a latent period of 10 years or more, and noneexceeded 15 years. This is not to say that muchdelayed recurrence is impossible. The literaturecontains instances. But it does appear uncommon:

there are enough long survivals in the London seriesto have provided examples if it were not.

In Table II operations of Grades I and II arecompared. The superiority of a Grade I operation,i.e., a sinus resection, with parasagittal tumours is,of course, self-evident. It must be emphasized,moreover, that the operations of Grade II includenone in which an obviously invaded sinus was leftuntreated: such operations are all classed in GradeIII. All these Grade II resections appeared satis-factory resections to the surgeons responsible, andthere were indeed many cases in which an entirelyfavourable prognosis was given. Table II also showsthe frequency of recurrence of the basal tumours;it appears relatively high both with operations ofGrade I and Grade II, which suggests that wherethere is no question of a major sinus being invaded,the diathermy current is a reliable weapon.The remaining operations, those of Grades III,

IV, and V, cannot be considered radical, and it maybe supposed that cases so treated will inevitablydevelop symptomatic recurrences, soon or late.

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Practical interest centres on the factor of time: theseless ambitious resections have given a few veryprolonged survivals. From the biological standpointthey also give a better concept of the growth rateof the meningiomas than can be obtained in anyother way.The 24 tumours treated by operations of Grade III

had, by definition, dural or extradural extensionswhich were not resected. In the majority these wereosseous: notably, nine were sphenoidal ridgetumours en plaque, with hyperostosis too extensivefor complete removal. Six were parasagittal tumours:in these, either the operation spared a venous sinusknown to be invaded, or it was carried out with noattention to the possibility of such invasion. In thewhole group there have so far been three verifiedrecurrences and four unverified, but almost in-dubitable. An eighth case is also at present undersuspicion. This is an incidence of only 29 %. More-over, the graph of survivals (Fig. 1) shows a fewvery good long-term results, mostly with patients inwhom the residue is hyperostotic bone. Sphenoidalridge tumours en plaque have indeed done well; theremay be radiological evidence of continued growthover the years, but in only one case has there beena serious recurrence.

In 51 cases, resection of the intradural tumourwas frankly incomplete. The operations rangedwidely in magnitude, from those in which the residuewas estimated as " only a thin shell" or " a coupleof tags ", to those in which at least half the tumourwas left in situ. Necropsies have, however, shownthat such estimates are wholly unreliable, and noeffort is made to subdivide these resections, whichare all classed in Grade IV. Various reasons dictatedthese incomplete procedures: most common was afear of injuring the great branches of the circle ofWillis. When the vascular relations of the tumourare so intimate a total eradication may be reallyimpossible, and it is therefore of importance to knowthe probable results of subtotal operations. Therehave in fact been 20 recurrences after operations ofGrade IV, mostly fatal, and in 12 instances un-verified. This gives a recurrence rate of 39 %, or44% ifcases treated in the last five years are excluded.Intercurrent disease appears to have carried offseveral other patients who might be expected tohave died of continued growth had they lived longer.A further hazard not brought out by these figures isthat the incompleteness of a resection may in itselfbe a danger; several post-operative deaths camefrom brain-stem compression unrelieved by thepartial excision of a deep-lying tumour. For all this,the limited resections have given a few pleasingresults. Thirteen patients (26%) have lived 10 years

or more; nine of these passed 15 years. The Londonseries provides two instructive illustrations of theindolence sometimes exhibited by these tumours.One man had a sphenoidal ridge tumour, of globaltype, about 5 cm. in diameter, adherent to thecavernous sinus and infiltrating into the pterygoidregion. It was found impossible to remove it all,and the surgeon responsible believed that the residue(which he charred with the diathermy electrode)represented a quarter of the whole. It was naturallyfeared that the patient would die from his tumour.In fact, however, for 18 years, he lived and diedof an accident; necropsy showed a residual menin-gioma no larger than a walnut. The other case wasa woman with a suprasellar meningioma. Abouttwo-thirds of this, by operative estimate, wereremoved in 1935. She was left with severe visual loss,but there is no evidence that this progressed, norany record of other complaints, until her death(suicidal) in 1955. Necropsy showed a massivesuprasellar meningioma; this must have beensilently growing for the previous 21 years, but wasstill not dangerous to life.

Simple decompression alone (operation of GradeV) may occasionally prolong life. It was the resortin a few cases, usually because of torrential bleeding.Nine survived more than six months, and two ofthese lived for seven and nine years respectively,before developing symptomatic recurrences.Some prominence has been given to these cases,

because they illustrate the extreme variations in thenatural history of the meningiomas. The indolenceexhibited by some is exemplified by these long sur-vivals: on the other hand, one of the frankly malig-nant recurrent tumours grew in 13 months from avestige invisible to the eye to a mass 6 x 5 x 4 cm. insize. This variability in the natural history of thedisease makes the general evaluation of any form oftreatment difficult. It also makes the possibilitiesof predicting the growth-rate of a particular tumourof great clinical interest.

The Pathological Basis of RecurrenceThe 246 cases in the Oxford series have given

material for an analysis of the pathology of themeningiomas. In 198 cases there are the operativedescriptions, often illustrated, and the biopsy speci-mens; in 41 there are also the records and specimensfrom necropsies done at varying times after opera-tion; and seven cases came to necropsy withoutprevious operation. Some of our patients died inremote hospitals, and it is likely that in severalinstances infiltration of adjacent structures escapedrecord. For this reason, the figures to be reportedprobably underestimate the infiltrative powers of thetumours.

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DONALD SIMPSON

The general pathology of the meningiomas hasbeen frequently described, and it would be impossibleto amplify such magnificent studies as that ofHenschen (1955). There are, however, certain pointsrelevant to the recurrence of these tumours whichneed emphasis.

First, their gross anatomy can make a totaleradication extremely difficult. When they aresmooth-surfaced, enucleation is easy; when they arenodular, as was the tumour shown in Fig. 2, anodule embedded in brain can be detached and over-looked. Good technique will, however, usually avoidthis. A similar danger is presented by the tendencyof global meningiomas to form miniature plaque-like extensions in the subdural space. This was foundin at least 21 cases (8 5%), excluding those 11meningiomas wholly en plaque in form. Usually thesubdural extension is a thin, flat fringe extendingfrom the periphery of the dural attachment for acentimetre or so, lying on but not infiltrating thearachnoid (Fig. 3). This fringe can adhere to themaninges after the removal of the main tumour.This has been actually seen to occur. A vestige ofsuch a fringe, if it were viable, would probably leadto a recurrence centred on the margin of the originaltumour, a situation in fact occupied by several of the

4.....

FIG. 2.-A sphenoidal ridge meningioma, showing the characteristicnodularity and the intimate relationship with the vessels of thecircle of Willis.

recurrent meningiomas in this series. In several casesthe subdural fringe was much thicker and far-spreading, even in one instance flowing over thewhole hemisphere from base to midline.But these formations (seen particularly with the

superficial tumours) are comparatively innocuous.Far worse manifestations of the tendency of menin-giomas to burrow along favourable tissue planes are

I ~x

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seen with the basal tumours. These are, as is wellknown, apt to envelop the great vessels of the circleof Willis, the cranial nerves, and the hypothalamus.This behaviour may make such tumours obviouslyinoperable. It could also defeat an apparentlysuccessful operation: unobtrusive extensions throughthe tentorial hiatus, around the carotid artery, oranterior to the pons might again be overlooked.There is, however, no definite evidence that this didoccur in this series; what did happen on a numberof occasions was catastrophic injury to great vessels,caused in an attempt at a perfect removal. Thisaccounted for at least eight of the 30 operative andpost-operative deaths in the Oxford series.These are all expressions of non-infiltrative

growth. It is, however, to be emphasized that themeningiomas, even those in other respects mostbenign, are also capable of infiltrative growth. Thedural attachments were invaded in a very largenumber of cases. It is indeed wise to assume thatthere is always dural penetration, although in a fewinstances none was actually seen in a limited exami-nation. Usually the dura wide of the actual area ofattachment is uninvaded; but rarely the meningiomacells may spread more diffusely and invade durathat is to the naked eye normal. However, this is ahighly unusual misfortune.

Invasion of a great dural venous sinus was con-firmed in 34 cases (14 %), and very strongly suspectedin a further six. In the majority, it was the superiorlongitudinal sinus. Invasion of this vessel was found

A.~~ ~ ~ ~ ~~t

FIG. 4.-A meningioma of the sphenoidal ridge invading ihe caver-nous sinus and the walls of the trigeminal ganglion.

(Haematoxylin and eosin x 90.)

in about 400% of the parasagittal tumours, and, aswill be seen, accounts for many recurrences afteroperations of Grade I1. Involvement of transverse,sigmoid, and cavernous sinuses was, however, notuncommon. In Figs. 4 and 5 sections of a very &ell-differentiated meningioma are seen, invading thecavernous sinus and even the walls of Meckel's cave.

Besides this manifestation of intradural spread,the meningiomas also exhibit transdural growth, andparticularly relevant is their tendency to grow acrossthe great dural septa, the falx, and the tentorium.This was found in 25 cases (10%), and this may wellbe an underestimate. Such spread is referred tohere as trans-septal extension, and is considered tobe of much importance.

Invasion of bone is a commonplace finding. Inthis series there were hyperostoses in some 79 casesand bony erosion in 21; there were thus gross bonyabnormalities (usually visible radiologically) in 36 %.In 50 cases there was microscopical proof of in-filtration of bone, and this again is certainly anunderestimate, because not all the hyperostoseswere examined adequately. Fig. 6 shows a typicalconical endostosis, partially (but not wholly) per-meated by a fibroblastic meningioma, microscopi-cally of apparent innocence (Fig. 7). Beside bone,many other extradural structures may be penetrated.The orbital cavity was invaded in seven cases, the

.-ft ':: W:-XF. s ':':..%! _. -w.

FIG. 5.-The same tumour. It is of endotheliomatous type, welldifferentiated and apparently of slow growth-rates.


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* 4

..~

FIG. 6.-The hyperostosis overlying a meningiomacconvexity. There is penetration by tumour cells.

(Haematoxylin-Vai

FIG. 8.-Invasion of the anterior pituitary by a subtemporal mening-

ioma.


temporalis muscle in six. The paranasal air sinuseswere involved in five cases, the middle ear in two.In one of the latter there was finally a neoplasticpolypus in the external auditory meatus, reminiscent

DONALD SIMPSON

.Bs: FIG. 7.-The same tumour. It is of fibroblastic type, well differentiated,''d.'. and apparently of very slow growth-rate.; ~~~~~~~~~~(Haematoxylin-Van Gieson x 90.)

FIG.6.-Thehypeostosisoverlyiftheencerebral50XI,)X

* V

FIG. 9.-A well-circumscribed meningioma and the adjacent brain.(Haematoxylin-Van Gieson x 160.)

of a jugular glomus tumour. The anterior pituitaryitself was invaded in one case (Fig. 8).

Finally, the brain may itself be invaded. This wasdenied by some of the earlier pathologists, notablyPenfield (1932), but it is incontestable. Usually themeningiomas were found clearly defined from brain,often by a " capsule " of flattened leptomeninges, asseen in Fig. 9. In nine cases (3-7 %) there was nosuch definition, but on the contrary a limited infil-tration of the brain tissue. Fig. 10 shows a fineexample. Kalbfleisch and Grebe (1937) justly presentthis as a possible cause of recurrence but it may atonce be said that its importance is limited. It is notonly rare, it is also less dangerous in practice thanwould be thought. The digital processes of tumourtend to adhere to the main mass, and in the casefrom which Fig. 10 was taken a complete removal



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FIG. 10.-Invasion of the brain by a meningioma of the cerebralconvexity, not otherwise of malignant type (operation specimen).


was in fact effected-complete as evidenced bynumerous sections made at necropsy through thetumour bed.These manifestations of invasive growth have been

given at length, because they appear to have beenresponsible for most of the recurrences in this series.They also show how far from benign, in the strictsense, the meningioma can be. Blatant malignancywas indeed presented by two tumours, whichmetastasized. One was a parasagittal meningioma,excised elsewhere, and treated here because of a localrecurrence. A Grade II resection was carried out,apparently successfully, but the patient died twoyears later with generalized visceral metastases, inlungs, liver, kidneys, and elsewhere. There was onlya minute intracranial recurrence at necropsy. Thiscase is to be published in full by Professor E. A.Linell, who has kindly allowed a preliminary report(Linell, 1955, personal communication). Thesecond case may be given in a little more detailbecause, besides its interest as an instance ofmetastasis, it is a microcosm of the problem ofrecurrence (Case 6 in Table V of Linell's series).

Illustrative Case ReportCatherine C. (R.I. No. 196859), aged 56, was first

admitted on September 27, 1954.She complained of headaches over the previous three

years and more severely over the previous two months,with recent mental confusion.

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Fio. 11.-A parasagittal meningioma with microscopic evidences ofvery active growth. Considered to be a very anaplastic fibro-endotheliomatous tumour, although evidence of fibroblasticactivity is lacking in this section.

(Haematoxylin-Van Gieson x 470.)

On examination she was drowsy, mildly demented, andwith a slight dysphasia; there was a minimal right hemi-paresis. There was papilloedema.Angiography showed a left frontal vascular tumour,

and the pathological diagnosis was of a meningioma,though some doubt was expressed over its innocence,because the arterial phase showed some rather irregularvessels.At operation on October 5 a Grade I excision of a

parasagittal frontal tumour was performed. To the nakedeye, this was a typical meningioma, if rather lobular, andit attached in characteristic fashion to the superiorlongitudinal sinus, invading without occluding it.

Histologically (Fig. 11) the tumour was an extremelyanaplastic growth, with many mitoses but fairly isomor-phous cells. Glycogen was present in many areas, andalso collagen, and there was some reticulin. It was con-sidered a meningioma, and microscopically of very rapidgrowth. It was feared that it would prove malignant.The patient tolerated the resection of the frontal

quarter or so of the superior longitudinal sinus well, andremained in good health for 12 months. She was re-admitted on November 15, 1955, however, because ofheadaches and progressive dementia developing rapidlyover the previous two weeks.On examination she was drowsy, apathetic, and

demented, more so than when first admitted. There wasno papilloedema, but the decompression bulged. Therewas now a left hemiparesis and bilateral grasp reflexes.Angiography showed a vascular bifrontal tumour,

much as before.At operation on November 22 a Grade I recurrent,

mainly left-sided bifrontal tumour was resected, with2 cm. of the remaining falx and sagittal sinus.

Histologically the appearances were similar, but thesigns of malignancy were even more marked.

31

AAAA



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..:.::

*:9 :.I

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FIG. 12.-An angioblastic meningioma of the cerebral convexity, also clinically benign. (a) Haematoxylin and eosin x 210. (b) Reticulin x 210.

Post-operatively the patient this time failed to improve,whether because of interference with the frontal venous

drainage or from some other cause is obscure. Sheremained stuporose and died on January 10, 1956.

Necropsy.-This showed no macroscopic or micro-scopic intracranial residue of tumour nor any primarygrowth elsewhere. There were, however, in the lungsthree small nodules, the largest 8 mm. in its greatestdiameter. Two were sub-pleural, one deep in the lungparenchyma.

Microscopically they are identical: they show spindleor polygonal cells, somewhat pleomorphic, and with muchcollagen in the stroma (Figs 12a, 12b). They do notexactly resemble the intracranial growth, but are nearlyrelated to it. The possibility that they are all independentmalignancies, or even that the intracranial tumour is a

metastasis from one of them, has of course arisen: butProfessors D. S. Russell and R. A. Willis, who have verykindly examined the microscopic preparations, concurin believing this most unlikely.

The purely histological study of the meningiomashas present relevance only as an index of their biologyand particularly of their disposition to recur. Classi-fications based on character of tissue differentiation,of which there are many (Henschen (1955) gives a

full review), have generally proved of little value. Inthis study, the tumours were at first classed as

endotheliomatous, fibroblastic, fibro-endothelioma-tous, angioblastic, and undifferentiated. This systemderives from the well-known classification of Blandand Russell (1938), and as far as possible the criteriawere theirs. It differs in that no separate identifica-tion of xanthomatous and myxomatous types ismade, and in the recognition of the " undifferen-

tiated " meningiomas. Table III shows the distribu-tion of these types, and their relation to recurrence.

TABLE IIIHISTOLOGY AND RECURRENCE IN THE OXFORD SERIES

(EXCLUDING 17 UNCLASSIFIABLE TUMOURS)

Endo- Fibro- Fibro- Angio- Undiftheioj eno- bias- bias- Uni-matous tei- tic tic tiated

matous tae

Total no. in the 132 39 37 12 5series

No. recurring after 12 3 2 - 2radical operation (3 twice) (both

twice)

Average survival 5 7 2-3 8-2 - 475before confirma- years years years yearstion, or diagnosisin unverified cases(counting individ-ual recurrencesseparately)

It may at once be said that this classification is oflittle biological significance, either in relation to theincidence of recurrence, or the disposition to infil-trate. None of the major groups has a monopoly ofmalignant behaviour or of innocence, except thatthe angioblastic meningiomas as here defined appearparticularly benign (vide infra). Only the small groupof undifferentiated meningiomas has peculiarproperties.

It is indeed notable that in each histological typethere are tumours varying widely in apparentactivity of growth, forming as it were a continuousspectrum. There are well-differentiated endothelio-matous tumours, with whorls and lobules of cellsrecalling arachnoid villi, and all the microscopic

32 DONALD SIMPSON

L.



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... ..<

FIG. 13.-Pulmonary metastasis from the same tumour.(a) Haematoxylin-Van Gieson x 70. (b) Haematoxylin and eosin x 160.

appearances of indolent growth. (Fig. 5 shows anexample.) But there are also a few tumours inwhich, though the cell type and cellular patternpermit classification as endotheliomatous, there ismuch nuclear pleomorphism and many mitoses.Similarly, the highly fibroblastic tumours show allgrades between the well differentiated growth ofFig. 7 and the highly anaplastic tumour seen inFig. 13. The angioblastic tumours are less easilysummed up. Some resemble, and are probably alliedto, the better-known cerebellar capillary haeman-gioblastomas (Fig. 14). Others show more maturevessels, and could be called angiomatoid (Fig. 15).Despite the frequent presence of giant cells, boththese groups appear microscopically of slow growthand behave innocently. This may appear surprising,

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for the angioblastic meningiomas have always had acertain notoriety (Bailey and Bucy, 1931). This isperhaps because most writers have comprehended asangioblastic tumours here designated undifferen-tiated.

In this series there were five tumours of peculiarand uniform character. To the naked eye they weretypical, rather vascular meningiomas, in conven-tional sites-subtemporal, parasagittal, cerebello-pontine, frontal cerebral, and cerebellar convexityrespectively. Under the microscope, they are seento be highly cellular and quite without organization(Fig. 1 6a). That is to say, they shcw neither

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FIG. 14.-A fibroblastic meningioma appearing to be of very rapid growth.(a) Haematoxylin-Van Gieson x 470. (b) Reticulin x 470.

33

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34 DONALD SIMPSON

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whorls, laminas, nor lobules. The cells are fairlyuniform, and in shape fusiform or multangular(Fig. 16a). Mitoses are seen in all five, and are verynumerous in two. Collagen is occasionally present,but much more impressive is the diffuse network ofreticulin seen throughout the substance of thetumour (Fig. 16b). Several show immature vessels,and this, together with the reticulin structure, atfirst suggested that the little group represents ananaplastic variant of the angioblastic meningioma.This may indeed be so, but no connecting transitionalforms have been found, and the vasoformativetendency is not constant. Any rapidly growing

FIG. 16.-An undifferentiated meningioma of the cerebral convexity.This tumour is the only one of this type which has not recurredas yet.(a) Haematoxylin and eosin x 210. (b) Reticulin x 210.

(c) Haematoxylin and eosin x 470.



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tumour may show poorly formed vasculature, andit seems best to designate as angioblastic only thosetumours in which the formation of vessels appearsthe chief and specific tissue differentiation. Otherterms were considered, but at present some non-committal expression seems best, and they arereferred to here as " undifferentiated ". Globus(1937) designated tumours apparently of similarhistology " meningiomas indifferentiale ". It seemsparticularly important to separate them from othermeningiomas, and especially from the angioblasticmeningiomas, because the prognosis is much worse.In two patients in the small group the tumours haverecurred fatally after radical excisions, one withwidespread terminal haematogenous metastases(vide supra). Two other patients have died followingsubtotal resections, one tumour recurring veryrapidly after a Grade III resection. Only one patientstill lives.

It will be seen that no attempt has been made toseparate the biologically malignant meningiomas onpurely microscopic grounds. Many writers havedone this, notably Craig (1927) and Turner et al.(1942). But Henschen (1955, p. 486) has very justlypointed out the difficulty of making any exact andconstant correlation. The best differentiated, mostindolent tumours may be extremely infiltrative, asFigs. 6-8 show. Very anaplastic meningiomas maynot recur; very well differentiated meningiomasmay do so, or even metastasize, as in Jurow's case(1941). It has appeared from this series that a clear-cut microscopic distinction between clinically benignand malignant meningiomas cannot be made. Shortof this, however, the microscopic study of themeningiomas has been a very helpful guide to theirbiological character, and particularly to their rateof growth. Numerous mitoses, lack of regulararrangement, and (though to a much lesser degree)nuclear pleomorphism suggest rapid growth; con-versely, regular whorl formation or organization inalveoli or laminae, many psammoma bodies, andan absence of mitoses indicate slow growth. Whena tumour is largely but incompletely excised,symptoms due to its continued activity are likely toappear within a couple of years if it is of rapidgrowth; if it is indolent, recurrence may be delayed10 years or more. (There are, of course, other factors,notably the size of the residuum and the situationof the tumour.) This is a simple proposition, andreference to Table III shows that it is partially valid.Eight recurrences took place with tumours con-sidered on their microscopic appearances to berapidly growing. The times elapsing before con-firmation of recurrence ranged between four yearsand 13 months, with a mean of two and a half years.On the other hand, 15 recurrences took place with

tumours whose histology suggests average or evenslow growth, and with these the mean time intervalwas six and a half years, with extremes of 13 yearsand 17 months. It is to be noted that the meningio-mas do not often change in their growth pattern.In the majority there is a striking constancy inhistological appearance and particularly in growthrate, even after intervals as long as 13 years. Onthe other hand, at least three tumours did show anapparent deterioration towards greater cytologicalmalignancy, which was borne out by their clinicalbehaviour.A final point to be emphasized is the tendency of

the meningiomas to multicentric growth. A secondprimary meningioma, such as the small tumourdepicted in Fig. 17, can simulate a recurrence of thetumour originally excised, if close enough to itanatomically. Volynkin (1955) has laid much stresson this, and it is undoubtedly a possibility to bekept in mind. But it is probably unusual. Multiplemengiomas are not common. Luyendijk's (1953)figure of 1-9 % is questionable, as it is not basedsolely on necropsy statistics; even so, in the smallseries of cases coming to necropsy here the incidencewas only 4 %.With this general appreciation as background, it

is interesting to consider the pathology of those19 tumours which have actually recurred after radical(Grade I or II) resections. In five, two recurrenceshave taken place, so it is necessary to analyse 24separate recurrences.The development of a recurrence must mean

either that the initial resection was inadequate, orthat the neoplastic change was multifocal, or thatviable tumour was accidentally implanted during anotherwise successful resection. In most of these 24recurrences, there is reasonably clear evidence toindicate that the first, most obvious, explanation iscorrect. In four, there appears to have been un-noticed trans-septal spread, across the falx in threeinstances and across the tentorium in one. In eightinstances, recurrence probably took place from aninvaded falx or superior longitudinal sinus. Onepatient certainly developed a recurrence from unsus-pected invasion of the orbital cavity. In two, perhapsthree, instances, there is reason to believe that therecurrence arose from intracerebral vestiges, andthe presumption must be that these represented in-filtration of the brain. Recurrence from invadedbone, over which Cushing (1938) appears to havebeen much concerned, seems unusual. In two casesmeningioma cells in the bone of the sphenoidal ridgemay perhaps have led to recurrences, but proof islacking. The extreme indolence of an hyperostosishas already been noted. In two other cases recur-rences developed which might from their anatomy

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Pi . .

FIG. 17.-Operation sketch of a meningioma of the cerebral convexity; a second small meningioma lies near it, and couid easilyescape notice.

have arisen either from an overlooked nodule, orfrom a fragment of subdural fringe, or from invadeddura: it is impossible to decide.The two other explanations of a recurrence are

hard to confirm or establish. Clear evidence of arecurrence from implanted fragments can only beobtained when the recurrence is in a scar (as in fiveof Cushing's cases), and this was never seen in theOxford series. But equally this mechanism cannotbe excluded in several of these cases, especially thosein which the tumour was removed piecemeal. Onesuch patient died a few days post-operatively, andserial sections showed a minute implant in thetumour bed; but the cells were obviously non-viable,and could not have led to a recurrence. Similarly,the possibility of multiple primary tumours is notalways to be excluded. In four instances the recur-rence was from two discrete foci. In two of theseit is quite possible that one of the recurrent tumourswas independent. Both patients had parasagittalmeningiomas; each had a recurrence from theinvaded falx and sinus and a second recurrencenearby but not really in the original operation field.

These are plausibly regarded as independent primarytumours, perhaps consequent on neoplastic "field"change in a wide area of dura; but they mightequally have arisen from vestiges of a subdural fringeon the periphery of the original tumour. There issimilar difficulty in interpreting some of the pub-lished reports of recurrent multiple meningiomas(e.g., Case 1 of Mufson and Davidoff, 1944).

ConclusionsThe incidence of recurrence will vary somewhat

with the experience of the surgeon, and still morewith his criteria of what constitutes an adequateoperation. Confusion will be lessened if somestandard assessment of the scope of the resections isused; the system employed here could doubtless bebettered, but has nevertheless appeared helpful bothfor individual prognosis and for comparative studies.The results reported here are probably representa-

tive, and they suggest that even with the most radicalsurgery recurrence is not a possibility to be ignored.When the tumour has been to the naked eye whollyremoved, together with its dural attachment and any

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obvious extradural extension (a Grade I resection),it would seem that the surgical ideal has beenachieved. Yet in this series the incidence of recur-rence in cases so treated was 9 %. Where the duralattachment is considered irremovable, as must oftenhappen, it is common practice to coagulate it, evento charring, with the diathermy cautery. If com-bined with a complete removal of the visible tumour(Grade II resection), this is generally considered anacceptable alternative to the more radical excision;but the incidence of recurrence following suchoperations was in this series 19%. It is clearly im-portant to distinguish between operations of Grade Iand Grade II, both for prognosis and in the presen-tation of results.The causes of recurrence are not particularly

mysterious, and have been well discussed byCushing (1938) and others. The material reportedhere suggests, however, that their relative importancehas not always been gauged correctly.

In the first place, there is a tendency to assumethat any meningioma which recurs is malignant.Innocence and malignancy are at best relative terms,and become particularly hard to apply with themeningiomas, tumours with which local infiltrationis so common and metastasis so rare. By anystandards, two of the 19 recurrent tumours studiedin this investigation were malignant, since theyformed haematogenous metastases. Four othertumours would have been regarded as malignant onhistological grounds by many, and certainly theirbiological characteristic has been aggressive andrapid growth. But in the other 13 there were neithermicroscopic nor biological peculiarities to dis-tinguish them from the great mass of meningiomaswhich did not recur.

It is more profitable to consider these recurrencesas the expression of a failure in surgery, a failure toeradicate microscopic infiltration or even grosserextension. It seems that unnoticed invasion of thewalls of a great venous sinus is the most commoncause of recurrence after seemingly successfuloperations, especially those of Grade II, but evenrarely those of Grade I, presumably because theinfiltration may be invisible. Unnoticed spreadacross a free dural septum is also an important causeof failure with Grade II resections. Microscopicinfiltration of brain and visible but unobstrusivepermeation of the subdural space are probablyimportant though rarer causes of recurrence. In-vasion of bone cannot be ignored, but it appears ofoverrated importance: when one recalls how fre-quently meningiomas are associated with hypero-stosis or bony erosion, it is surprising how rare is arecurrence clearly arising from bone. There isindeed in the behaviour of hyperostoses after4

Grade III resections good evidence to suggest thatmeningiomatous cells in bone are particularly indo-lent. Nevertheless, trouble may come from invadedbone, especially in the region of the orbit. Finally,surgery may fail when the disease is multifocal:when neoplastic change is not restricted to one point,and there are multiple meningiomas. This wouldappear comparatively rare, but there is need forfurther information.

These failures are, of course, often ineluctable:they express the limitations imposed on the surgeonby the need to conserve brain function. It is possibleto carry the line of excision through normal tissuewhen dura and bone are concerned; it is usually notpossible to do such a " cancer operation " throughnormal brain, though Fincher (1954) mentions doingso with one malignant growth. Routine blockresection of the great venous sinuses would greatlydecrease the incidence of recurrence, but at a pro-hibitive price in immediate disability or even (Jaeger,1942, 1951) in death.

If these propositions are accepted, there are certainpractical corollaries.

Surgery should be as radical as is safe. In general,contemporary practice probably goes as far as ispossible. There can be no doubt that when ameningioma attaches to the falx or the tentoriumits attachment can and ought to be removed. Whena meningioma attaches to a great venous sinus theproblem becomes much more difficult. A Grade Iresection is impossible when the cavernous or thestraight (vide Castellano and Ruggiero, 1953) sinusis involved. The transverse sinus can apparently beresected, though this was not done in any case inthis series. The superior longitudinal sinus wasresected en bloc on only 17 occasions in the Oxfordseries, and in general the results bear out Olivecrona's(1947) dictum that when the sinus is occluded itmay always be excised, but that when it is patentexcision is safe only in the frontal third. No questionrequires nicer surgical judgment than this, and it issignificant that Olivecrona's vast experience (Hoesslyand Olivecrona, 1955) is making him increasinglyconservative. When a meningioma involves bone,the area of macroscopic abnormality ought clearlyto be excised, but in this series it has not appearednecessary to boil the bone flap. When a meningiomahas actually recurred experience here justifies asecond operation on the most radical scale, even atgreater hazard than would ordinarily be accepted.This is because of the greater likelihood of a secondrecurrence. Some very gratifying results have beenachieved by such operations. Of the multiplemeningiomas, it can only be urged that their possiblepresence must be kept in mind, especially in inter-preting the preliminary radiological studies.

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At the same time it is important to recall that sub-total resection can give very useful palliation; whena radical operation is obviously dangerous to life orto function, a limited procedure may be preferable.This is particularly so with parasagittal tumours,when the posterior portion of the superior longi-tudinal sinus is invaded but patent. A resectionof Grade III may give many years' respite, and permita later operation of Grade I to be done with im-punity when the sinus has become occluded. Aftersubtotal resections generally, there is also a case forirradiation. Most authors deny that these tumoursare sensitive, and experience here has on the wholebeen discouraging. Twenty-eight tumours have beenirradiated for various reasons, and although assess-ment is difficult there has been little evidence ofpermanent benefit. In one case, there is unhappilyproof of detriment, in the shape of a cripplingradiation necrosis. Nevertheless, in one or twotumours there appears to have been a slight response,and radiotherapy may perhaps be warranted whenexcision is certainly incomplete and the meningiomaof rapid growth.

Since future recurrence can never wholly beexcluded, the pathologist reporting on a biopsyshould make his assessment with recurrence in mind.It has appeared in this clinic that the undifferentiatedmeningiomas are definitely of bad prognosis, andthat they should be separately identified. Even moreimportant is an estimate of the growth-rate of thetumour, in making which the presence of mitosesseems of chief moment. Such an estimate, thoughsubjective, has proved of practical value, and is moreflexible than an attempt to divide the meningiomasinto microscopically malignant and innocent groups.It is possible that the angioarchitecture of themeningiomas, as demonstrated by cerebral angio-graphy, may be correlated with the methods of con-ventional pathology in obtaining a final assessmentof the biological character of a tumour. Lorenz(1940) has described the angiographic appearancesof meningeal sarcomas as characteristic. Investiga-tion into this possibility has been begun, but thereare many pitfalls, and at present it seems best toreserve judgment.The clinical diagnosis of a recurrence presents

some interesting problems, and can be extremelydifficult. Generalization is hard; but it may be saidthat the recurrent tumours (except those in theposterior fossa) are not commonly associated withthe manifestations of raised intracranial pressure.Even the craniectomy decompression (if provided)may be indrawn, and papilloedema is comparativelyunusual. Usually the patients' complaint is of someprogressive neurological deficiency, motor, visual,or mental, and here diagnosis should usually be easy.

It must, however, be remembered that many ofthose patients have entered the age-period of arterio-sclerosis, and that the bed of a successfully removedm-ningioma may be a locus minoris resistentiae:progressive cerebral arteriosclerosis may increase apre-existing neurological deficiency. Still greaterdifficulty arises with those patients whose onlysymptom is epilepsy. This is a regrettably commoncomplaint even after a successful excision. It wasfound in 43% of cases in the Oxford series. Only ina minority, less than a quarter, did the fits herald arecurrence; in the remainder they were presumablythe manifestation of gliosis in the cerebral cortex.A practical guide is in the time relations: the epilepsyof a recurrence is delayed, insistent, and progressivelyharder to control whereas the epilepsy of gliosis isearly in onset (within the first year or so), and tendsto diminish in severity as the years go by. There are,however, exceptions to this dictum, and when thereis doubt intelligent procrastination is usually war-ranted. Special neuroradiological investigations willusually give the answer but it must be said in warningthat air studies sometimes are deceptive. This isbecause the recurrent tumour's effect as a space-occupying lesion can be offset if there is undue spaceto be taken up, and this illusion is maintained whenthe original operation has been followed by localcerebral atrophy. So far angiography has neverfailed to demonstrate the recurrence, but here tooit is possible that an avascular tumour might showno definite displacement of the arterial and venousanatomy. The most important factor in diagnosingthese recurrences is awareness of their possibilityand as far as can be determined their likelihood. Inthe average case, recurrence will be unlikely butalways possible: unlikely enough to permit reassur-ance even when minor symptoms cause alarm to thepatient, but possible enough to demand sustained,tactful watchfulness.

SummaryThe results obtained in two series of intracranial

meningiomas, one of 235 cases and one of 97 cases,are analysed to determine the incidence of recurrenceafter surgical excision.A system of grading according to the scope of the

resection is presented, and is applied to those cases,265 in all, surviving more than six months.

Following 90 operations of Grade I, in which thetumour, its dural attachment, and all apparentextradural extensions are resected, there appear tohave been eight recurrences (9 %).

Following 114 operations of Grade II, in whichthe visible tumour is totally removed, but its duralattachment merely coagulated with the endothermy

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cautery, there were 18 recurrences, or 19% if casestreated in the last five years are excluded.These recurrences became manifest after an

average period of five years. Long-delayed recur-rence, though clearly possible, appears unusual.

After operations known to be incomplete (GradesIII-V) the incidence of symptomatic recurrence isnaturally much greater, but it is important to notethat a number of patients treated by limited excisionshave been given long periods of relief.

It is emphasized that in the clinical sense, menin-giomas may be benign, locally invasive, or franklymalignant. The frequency of local infiltration isstressed: infiltration of venous sinuses was found in15% of cases, of bone in 20 %, and of brain in 3 7 %.Haematogenous metastasis was seen in two patients.

Histological assessment has proved of much valuein predicting behaviour but its limitations are con-

siderable. A small group of undifferentiated vascular,reticulin-forming meningiomas has been identifiedas particularly unfavourable.

Nineteen tumours recurring after seemingly com-

plete resection are considered. While two were

highly malignant and four others showed micro-scopic signs of rapid growth, 13 were in no way

remarkable.The chief causes of recurrence appear to have

been unnoticed invasion of a dural venous sinus, andunsuspected spread across a free dural septum.Detached nodules of tumour, fragments of thesubdural fringe often seen in meningiomas, infiltra-tion of bone, and the presence of multiple primarytumours are other occasional causes of recurrence.

The practical implications of these findings, bothin treatment and in prognosis, are briefly discussed.

This research was carried out with the aid of a grantfrom the United Oxford Hospitals. The cases in theLondon series were made available by the kindness ofMr. D. W. C. Northfield and the Staff Medical Com-

mittee of the London Hospital. I am most grateful toMr. J. Pennybacker and to Drs. P. Daniel and S. J.Strich for much assistance in the preparation of thispaper; I would also like to thank Miss A. Arnott, Dr.R. H. Cowdell, and Mr. E. L. P. Tugwell for the illustra-tions and photomicrographs.

REFERENCESBailey, P., and Bucy, P. C. (1931). Amer. J. Cancer, 15, 15.Ballance, C. A. (1907). Some Points in the Surgery of the Brain and

its Membranes. Macmillan, London.Bland, J. 0. W., and Russell, D. S. (1938). J. Path. Bact., 47, 291.Castellano, F., and Ruggiero, G. (1953). Acta radiol. (Stockh.),

Suppl. 104.Christensen, E., Klaer, W., and Winblad, S. (1949). Brit. J. Cancer,

3, 485.Craig, W. McK. (1927). Surg. Gynec. Obstet., 45, 760.Cross, K. R., and Cooper, T. J. (1952). J. Neuropath., 11, 200.Cushing, H. With the collaboration of Eisenhardt, L. (1938). Menin-

giomas. Thomas, Springfield, Illinois.Fincher, E. F. (1954). Surg. Clin. N. Amer., 34, 1037.Globus, J. H. (1937). Arch. Neurol. Psychiat. (Chicago), 38, 667.

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